7. Project Summary/Abstract Nephrolithiasis is treated by surgery or watchful waiting, and in either course, patients are exposed to radiation in multiple imaging exams. We propose noninvasive treatment and non-ionizing imaging options and seek to validate the clinical benefit of these new options. Our invention is ultrasound (US) technology that operates with a standard probe and diagnostic US interface. Our imaging technology addresses three limitations of conventional US imaging for nephrolithiasis: poor sensitivity and specificity, inaccurate measurement of stone size, and variable performance among operators. Our US detection of stones is based on our new findings on the etiology of the US twinkling artifact, and Aim 1 will test the receiver operator characteristics as well as inter- operator variability of the new detection technology versus observation in computer tomography (CT) and ureteroscopy (URS). Aim 1 will also test outcomes of using the technology to guide comminution of stones by shock wave lithotripsy, and our detection sensitivity will be augmented by a new technology, electromagnetic acoustics. Our sizing technology is based on enhancing the image of the stone's shadow and measuring the width of the shadow not the stone. Sizing, as with stone identification within the image, is done automatically to reduce the operator dependence. In Aim 2, size measurement will be compared to the actual size of stones that will be removed by URS. The technology will be further enhanced by time reversal acoustics and tested to resolve subclinical stones not likely to be measured accurately by CT. Additionally, our technology adds the capability to use the US waves from the probe to reposition stones in the kidney. The clinical benefit of this ultrasonic propulsion (UP) will be tested in Aim 3. The clearance rate of residual fragments expelled from the kidney by UP will be tested versus untreated human subjects. Also in Aim 3, UP will be tested for relieving pain and hydronephrosis by displacing emergent obstructing stones from the uretero-pelvic junction retrograde to the kidney. In Aim 4, we will test for reduction in recurrence among human subjects by removing asymptomatic subclinical stones from the kidney with URS or UP. As such, this proposal possesses innovation with the potential to revolutionize treatment. Stone disease is significant, affecting 10% of the population, and our inventions stand to reduce patient radiation exposure, reduce patient pain, reduce emergency room usage, avoid surgeries, and cut costs for a significant subset of stone patients without precluding existing options. This proposal is likely to succeed because it focuses on specific, testable, clinical validation of a demonstrated prototype. Lastly, the proposal is part of a closely collaborative, interdependent Program Project coordinated by Core A, and fits within a broader treatment revolution. Core B has devised and will administer the proper statistical framework for the studies. With Project 2, our imaging will be used to guide a new noninvasive stone comminution technology called burst wave lithotripsy, and with Project 3, UP will be used to improve current SWL and prevent surgeries by prophylactically removing subclinical stones.